Background: The current study was conducted to determine if efavirenz (EFV) or atazanavir/ritonavir (ATV/r)-based combination antiretroviral therapy (cART) impacted steady-state atovaquone plasma concentrations in human immunodeficiency virus (HIV)-infected patients receiving treatment doses of atovaquone.
Methods: Thirty HIV-infected volunteers were recruited, 10 taking no cART and 10 each taking cART that included EFV or ATV/r. Subjects were randomly assigned to atovaquone 750 mg twice daily (BID) for 14 days followed by atovaquone 1500 mg BID for 14 days, or vice-versa, with a washout period in between. On day 14 of each phase, blood was sampled for pharmacokinetic studies, and the area under the concentration-time curve (AUCτ) and average concentration (C avg) were calculated and compared using an unpaired t test.
Results: Twenty-nine subjects completed both dosing cohorts. Subjects receiving EFV-based cART had 47% and 44% lower atovaquone AUCτ than subjects not receiving cART at atovaquone doses of 750 mg BID and 1500 mg BID, respectively (P≤ .01). Only 5 of 10 subjects receiving EFV-based cART plus atovaquone 750 mg BID had an atovaquone C avg>15 µg/mL, which has previously been associated with successful treatment of Pneumocystis jirovecipneumonia. AUCτ and Cavg did not significantly differ for concurrent ATV/r for 750 mg BID or 1500 mg BID when compared to the group not receiving cART. Nine of 10 subjects not receiving cART, 8 of 10 subjects receiving ATV/r, and 2 of 10 subjects receiving EFV in combination with atovaquone 750 mg BID achieved an atovaquone C avg>18.5 µg/mL, a concentration that has previously been associated with successful treatment of Toxoplasmaencephalitis (TE).
Conclusions: These data suggest that the currently recommended dose of atovaquone 750 mg BID for treatment of mild to moderate PCP may not be adequate in patients receiving concurrent EFV. Furthermore, doses lower than the currently recommended dose of 1500 mg BID may achieve plasma concentrations adequate to treat TE in HIV-infected patients not receiving EFV.
Clinical Trials Registration: NCT01479361.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4803107 | PMC |
| http://dx.doi.org/10.1093/cid/ciw028 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
BAY 2413555 is a novel selective and reversible positive allosteric modulator of the type 2 muscarinic acetylcholine (M2) receptor, aimed at enhancing parasympathetic signaling and restoring cardiac autonomic balance for the treatment of heart failure (HF). This study tested the safety, tolerability and pharmacokinetics of this novel therapeutic option. REMOTE-HF was a multicenter, double-blind, randomized, placebo-controlled, phase Ib dose-titration study with two active arms.
View Article and Find Full Text PDFJuvenile Incarceration in an Adult Facility and Violent Victimization During Adulthood.
J Adolesc
December 2024
Center for Legal Systems Research, RTI International, Research Triangle Park, North Carolina, USA.
Introduction: A growing body of research indicates that being incarcerated in an adult jail or prison as a juvenile can elevate one's exposure to adverse childhood experiences, including violent and sexual victimization and neglect, and may lead to several long-term difficulties. This study investigates the relationship between being confined in an adult jail or prison as a minor and experiencing violent victimization as an adult.
Methods: Data from the National Longitudinal Survey of Youth-1997 cohort were used in the study.
Low-Dose Emicizumab Versus Low-/Intermediate-Dose Factor VIII Secondary Prophylaxis for Noninhibitor Haemophilia A Patients With Severe Bleeding Phenotype.
Haemophilia
December 2024
Division of Pediatric Hematology and Oncology, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University and King Chulalongkorn Memorial Hospital, Bangkok, Thailand.
Background: Subcutaneous emicizumab, a factor VIII (FVIII)-mimicking bispecific monoclonal antibody, can effectively prevent bleeds in haemophilia A (HA) patients with/without inhibitors; however, its standard-dose regimens are financially burdensome. Low-dose emicizumab prophylaxis may alternatively be applied to noninhibitor HA patients in resource-limited settings.
Methods: During 2023, Thai patients with noninhibitor severe HA or moderate HA with severe bleeding phenotype (historical annualized bleeding rate [ABR] >5 bleeds/year before regular FVIII prophylaxis) who received low-/intermediate-dose FVIII secondary prophylaxis ≥8 months were enrolled.
Diaphragmatic Nerve Paralysis After Redo Aortic Valve Replacement That Improved Over Time and Led to Successful Ventilator Weaning: A Case Report.
Cureus
November 2024
Cardiovascular Surgery, Sapporo Medical University, Sapporo, JPN.
We report a 75-year-old female with a history of two heart operations: aortic valve replacement (St. Jude Medical 21 mm) at the age of 44 years for severe rheumatic aortic stenosis and mitral valve replacement (Carbomedics 29 mm) at the age of 51 years for rheumatic mitral regurgitation. Decades later, she presented with exertional dyspnea.
View Article and Find Full Text PDFEarly Patient Outcome and Left Ventricular Function After Mitral Valve Replacement Using a Tilting Disc Mechanical Valve With Total Preservation of Mitral Valvular Apparatus.
Cureus
November 2024
Internal Medicine, Shri Ram Murti Smarak Institute of Medical Sciences, Bareilly, IND.
Introduction The study aimed to retrospectively evaluate the early patient outcome and left ventricular function after mitral valve replacement with a tilting disc valve and total preservation. Patients and methods This retrospective observational study includes patients who underwent mitral valve replacement using a tilting disc valve with total preservation of mitral valvular and subvalvular apparatus from July 2021 to August 2022 at a single center. Results The data were reviewed retrospectively for age, sex, comorbidities, operating time, aortic cross-clamp time, cardiopulmonary bypass time, preoperative and postoperative left ventricular ejection fraction, mean gradient across the mitral valve, left ventricular diameter, left atrial size, atrial fibrillation, complications, mortality, and early patient outcome.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!